Epilepsy and its related syndromes may be classified according to whether the associated seizures are partial or generalized, and whether the etiology is idiopathic or symptomatic/cryptogenic. Several important syndromes can be further grouped according to age of onset and prognosis.
Epilepsy is a chronic brain disease in which epileptic seizures are the predominant feature. Generally, most epilepsies and diseases associated therewith are difficult to treat, since epilepsies are not etiologically elucidated. Thus, administration of an antiepileptic agent is a common approach toward suppressing epileptic seizures or inhibiting propagation of focal seizures to other portions.
The older established antiepileptic drugs (AEDs) such as phenyloin, carbamazepine, clonazepam, ethosuximide, valproic acid and barbiturates are widely prescribed but suffer from a range of side effect. Furthermore, there is a significant group of patients (20-30%) that are resistant to the currently available therapeutic agents. Fifty million people in the world have epilepsy, and there are between 16 and 51 cases of new-onset epilepsy per 100,000 people every year. A community-based study in southern France estimated that up to 22.5% of patients with epilepsy have drug-resistant epilepsy. Patients with drug-resistant epilepsy have increased risks of premature death, injuries, psychosocial dysfunction, and a reduced quality of life.
One study showed that the use-dependent blockade of the fast sodium current in dentate granule cells by carbamazepine was lost in hippocampi resected from patients with carbamazepine-resistant temporal-lobe epilepsy, although this finding did not extend to lamotrigine, which has a pharmacologic action similar to that of carbamazepine. Altered expression of subtypes of the γ-aminobutyric acid type A (GABAA) receptor has also been observed in patients with drug-resistant temporal-lobe epilepsy. Whether these changes result in reduced sensitivity to antiepileptic drugs that act on the receptor is unknown.
Since 1989 several new drugs have been launched, including felbamate, gabapentin, lamotrigine, oxcarbazepine, tiagabine, topimarate, vigabartrin, zonisamide and levetiracetam. While many of new drugs AEDs show improved efficacies and side-effect profiles, patients with intractable epilepsy remain untreated. Because of the need to individualize therapy, no rigid set of guidelines can be applied to determine medical intractability. There is still a need for improved medication.